HOXA13

homeobox A13, the group of HOXL subclass homeoboxes

Basic information

Region (hg38): 7:27193503-27200091

Previous symbols: [ "HOX1J", "HOX1" ]

Links

ENSG00000106031 ∙ NCBI:3209 ∙ OMIM:142959 ∙ HGNC:5102 ∙ Uniprot:P31271 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hand-foot-genital syndrome (Strong), mode of inheritance: AD
• hand-foot-genital syndrome (Definitive), mode of inheritance: AD
• hand-foot-genital syndrome (Moderate), mode of inheritance: AD
• hand-foot-genital syndrome (Supportive), mode of inheritance: AD
• Guttmacher syndrome (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hand-foot-genital syndrome; Guttmacher syndrome; Hand-foot-uterus syndrome	AD	Renal	The disorder may be recognizable in the majority of individuals, but individuals are at risk of renal findings such as unrecognized vesicoureteral reflux, which can cause renal damage, and prophylactic/treatment measures can be beneficial	Genitourinary; Musculoskeletal; Renal	5450271; 8484413; 9020844; 10839976; 11968094; 12073020; 12414828; 12676922; 19591980; 20301596; 21549968

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HOXA13 gene.

• not_provided (121 variants)
• Hand-foot-genital_syndrome (63 variants)
• Inborn_genetic_diseases (54 variants)
• Guttmacher_syndrome (53 variants)
• HOXA13-related_disorder (26 variants)
• not_specified (6 variants)
• Congenital_heart_disease (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HOXA13 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000522.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	45	5	56
missense	1	2	111	10		124
nonsense	3	1	1			5
start loss						0
frameshift	1	2	1			4
splice donor/acceptor (+/-2bp)						0
Total	5	5	119	55	5

Highest pathogenic variant AF is 0.00000560017

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HOXA13	protein_coding	protein_coding	ENST00000222753	2	6604

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.955	0.0448	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.558	143	163	0.877	0.00000775	2461
Missense in Polyphen		39	56.4	0.69148		731
Synonymous	-1.09	81	69.4	1.17	0.00000358	834
Loss of Function	2.89	0	9.73	0.00	4.23e-7	123

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Sequence-specific, AT-rich binding transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior- posterior axis.
• Disease: DISEASE: Hand-foot-genital syndrome (HFG) [MIM:140000]: A disorder characterized by limb and genitourinary anomalies. Clinical features include small feet with unusually short great toes and abnormal thumbs. Females with the disorder have duplication of the genital tract. {ECO:0000269|PubMed:10839976, ECO:0000269|PubMed:12073020, ECO:0000269|PubMed:24934387, ECO:0000269|PubMed:26590955}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Guttmacher syndrome (GUTTS) [MIM:176305]: Dominantly inherited combination of distal limb and genital tract abnormalities. It has several features in common with hand-foot- genital syndrome, including hypoplastic first digits and hypospadias. Typical features not seen in hand-foot-genital syndrome include postaxial polydactyly of the hands and uniphalangeal second toes with absent nails. {ECO:0000269|PubMed:11968094}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Haploinsufficiency Scores

• pHI: 0.689
• ghis: 0.425

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.585

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hoxa13
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype; skeleton phenotype; renal/urinary system phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype; vision/eye phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: hoxa13a
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• Biological process: skeletal system development;regulation of transcription by RNA polymerase II
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;sequence-specific DNA binding